Reduced kappa-opioid activity in a rat model of cholestasis

Increased endogenous opioid activity has been implicated in cholestatic pruritus. In the present study, we have further defined the involvement of opioids in cholestasis. Rats underwent either bile duct ligation or a sham operation. Five days after surgery, brains were removed and agonist-stimulated...

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Bibliographic Details
Published in:European journal of pharmacology 2005-08, Vol.518 (2-3), p.182-186
Main Authors: Inan, Saadet, Cowan, Alan
Format: Article
Language:English
Subjects:
[35S]GTPγS binding
Animals
Binding, Competitive - drug effects
Biological and medical sciences
Brain - metabolism
Cholestasis
Cholestasis - blood
Cholestasis - metabolism
Cholestasis - pathology
Dialysis Solutions - chemistry
Disease Models, Animal
Dynorphins - analysis
Dynorphins - blood
Dynorphins - pharmacology
Enkephalin, Leucine - analysis
Enkephalin, Leucine - blood
Gastroenterology. Liver. Pancreas. Abdomen
Guanosine 5'-O-(3-Thiotriphosphate) - metabolism
Hypothalamus - metabolism
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Microdialysis
Oligopeptides - analysis
Oligopeptides - blood
Opioid system
Other diseases. Semiology
Pharmacology. Drug treatments
Pruritus
Rat
Rats
Rats, Sprague-Dawley
Receptors, Opioid, kappa - agonists
Receptors, Opioid, kappa - metabolism
Sulfur Radioisotopes
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Summary:Increased endogenous opioid activity has been implicated in cholestatic pruritus. In the present study, we have further defined the involvement of opioids in cholestasis. Rats underwent either bile duct ligation or a sham operation. Five days after surgery, brains were removed and agonist-stimulated [35S]GTPγS binding was measured in ten brain regions. Serum endomorphin-2, leu-enkephalin and dynorphin A levels were measured using ELISA on day five. Microdialysis to the dorsal hypothalamic area was conducted in the same animal before and after cholestasis. Dialysate endomorphin-1, leu-enkephalin and dynorphin A levels also were measured. Delta- and kappa-stimulated binding was significantly decreased in cholestasic animals compared to controls in the dorsal hypothalamic area. The serum dynorphin A level was lower in the cholestasic group than in controls (2.56±0.09 and 3.29±0.22 ng/ml, respectively, P
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2005.06.025